克伦特罗在猪体内的生物利用度及药物动力学研究

６头体重４７．００±４．５７ｋｇ（Ｘ±Ｓ）的健康长白和大白杂交猪，拉丁方设计试验，按４ｍｇ／ｋｇ静注、肌注和内服克伦特罗，高效液相色谱法检测血浆中药物浓度，ＭＣＰＫＰ药代动力学程序处理药时数据。静注给药的药代动力学参数是：ｔ１／２α０．６２±０．１２ｈ，ｔ１／２β４．８７±１．５６ｈ，Ｖｄ（ａｒｅａ）４．４８±０．５６ｌ／ｋｇ，ＣｌＢ０．６３±０．１１ｌ／ｋｇ／ｈ，ＡＵＣ６．３９±１．２７μｇ／ｍｌ．ｈ。肌注给药的药动学参数是：ｔ１／２Ｋａ０．２２±０．１０ｈ，ｔ１／２α０．５６±０．２１ｈ，ｔ１／２β４．２５±１．１０ｈ，ｔｍａｘ０．６０±０．１３ｈ，Ｃｍａｘ１．２７±０．３５μｇ／ｍｌ，ＡＵＣ５．４８±１．２９μｇ／ｍｌ．ｈ，Ｆ８５．４０±４．６９％。内服给药的药动学参数是：ｔ１／２Ｋａ０．２８±０．１５ｈ，ｔ１／２Ｋｅ３．１５±０．３６ｈ，ｔｍａｘ１．４６±０．１９ｈ，Ｃｍａｘ０．６５±０．１３μｇ／ｍｌ，ＡＵＣ３．９３±０．９９ｍｇ／ｌ．ｈ，Ｆ６１．０２±１０．９０％。肌注给药的生物利用度与内服比较，差异极显著（Ｐ＜０．０１）。     

Toxicokinetics of the active doxorubicin metabolite, doxorubicinol, in sulphur-crested cockatoos (Cacatua galerita)

The pharmacokinetics of doxorubicinol, a cytotoxic metabolite of the anticancer drug, doxorubicin, were studied in four healthy sulphur-crested cockatoos (Cacatua galerita) after a 20 min intravenous infusion of 2 mg/kg. Plasma doxorubicinol concentrations were measured by HPLC. The pharmacokinetic parameters were estimated using a non-compartmental method. The mean (+/- SD) peak concentration was 8341 +/- 3132 microg/L at 17.5 +/- 5.0 min after the start of the infusion, and doxorubicinol concentrations declined biexponentially to 154.3 +/- 34.5 microg/L, 40 min after the end of the infusion. Systemic clearance was 0.940 +/- 0.473 L/h/kg, mean residence time was 0.165 +/- 0.133 h, and steady-state volume of distribution was 0.123 +/- 0.0526 L/kg. The terminal half-life was 0.660 +/- 0.611 h. Detectible but unquantifiable concentrations of doxorubicinol were present in the plasma ultrafiltrate of two birds during the infusion, indicating very extensive plasma protein binding. Physiological, haematological and biochemical monitoring over 3 weeks showed that doxorubicinol at a single infused dose of 2 mg/kg caused no toxicities of major concern.     

An in vivo analysis of the therapeutic and synergistic properties of Chinese medicinal formula Yin-Chen-Hao-Tang based on its active constituents

6,7-Dimethylesculetin (D), geniposide (G) and rhein (R) are the three major active ingredients of Yin-Chen-Hao-Tang (YCHT), a famous Chinese herbal formula, which has been shown to be clinically effective for treating hepatic injury (HI) syndrome. The present study was conducted to investigate the therapeutic and synergistic effects of COC (combination of D, G and R) on HI rats by combining pharmacokinetic with biochemical analysis strategy. Plasma was analyzed by using reversed-phase high performance liquid chromatography (RP-HPLC). Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were built to evaluate the therapeutic and synergistic effects of COC at the biochemical level. Here, we report that the COC combination could increase the plasma level, slow elimination rate, exert a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of HI. Overall, this beneficially accounts for the popular view that traditional Chinese medicine (TCM) formula usually takes multi-component to exert their therapeutic effects. We suggest that dissecting the mode of action of clinically effective formula to be capable of producing a sufficient effect at low doses.     

Permeability determination and pharmacokinetic study of nobiletin in rat plasma and brain by validated high-performance liquid chromatography method

In the present study, we are reporting permeability and pharmacokinetics of nobiletin in rat plasma and brain, using a validated reverse phase high performance liquid chromatographic method. Protein precipitation method was used for the extraction of nobiletin and coumarin (IS) from rat plasma and brain tissue. The system was run in isocratic mode with mobile phase consisting of potassium dihydrogen ortho-phosphate (pH 4.5; 0.04 mM) and acetonitrile in ratio of 50:50, v/v. The total chromatographic run time was 9.0 min. The method was proved to be accurate and precise at linearity range of 0.05–10 μg/mL with a correlation coefficient (r) of ≥ 0.994 in rat plasma and ≥ 0.995 in rat brain. The intra- and inter-day precision and accuracy values are found to be within the assay variability limits as per the FDA guidelines. Nobiletin was found stable in the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and long term storage in a freezer at − 70 ± 10 °C. Maximum concentrations of nobiletin in both plasma and brain were observed at 1 h after single oral dosing (50 mg/kg). The maximum concentration in plasma and brain were 1.78 and 4.20 μg/mL, respectively. The AUC_0–t in plasma and brain were 7.49 and 20.66 μg·h/mL, respectively. The mean elimination half life (t_1/2) in plasma and brain were 1.80 and 11.42 h, respectively. The Parallel Artificial Membrane Permeability Assay (PAMPA) permeability of nobiletin was found to be high at both pH 4.0 and 7.0.     

牙鲆仔鱼在混合饵料期的摄食能力及饵料选择性

研究了牙鲆仔鱼在轮虫、卤虫无节幼体混合饵料期的摄食能力及饵料选择性指标,结果表明,在开口后的第8天、第10天、第11天以轮虫为喜好性饵料,且最适的密度为10ind/mL,在开口后第10天对卤虫无节幼体开始有了一定的摄食能力;在开口后的第13天以后以卤虫无节幼体作为喜好性饵料;在开口后第15天开始放弃对轮虫的选择,可以以卤虫无节幼体作为唯一的食物来源;在轮虫、卤虫无节幼体混合饵料期,轮虫的最适密度是7～10ind/mL,卤虫无节幼体的最适密度是5～7ind/mL。     

牙鲆Follistatin cDNA的克隆与序列分析

为研究海水鱼中Follistatin基因的序列特征,从受精后67 h的牙鲆受精卵中克隆获得牙鲆Follistatin基因cDNA序列,并对其进行序列分析.结果表明,在牙鲆中并没有发现Follistatin基因的可变式剪切现象;牙鲆Follistatin基因cDNA序列全长963 bp.序列分析结果显示:牙鲆与Takifugu rubripes的亲缘关系最近.Follistatin蛋白中高度保守的半胱氨酸和甘氨酸残基的生物学功能可能是维持蛋白空间结构的稳定.     

牙鲆稚鱼对几种化学消毒剂的敏感性研究

研究了6种化学消毒剂对牙鲆Paralichthys olivaceus稚鱼的最低致死浓度范围、死亡速度、半致死浓度（LC50）和安全浓度。牙鲆稚鱼对6种化学消毒剂的敏感性依次为：孔雀石绿＞次氯酸钠＞二氧化氯＞净水剂1号＞硫酸铜合剂＞高锰酸钾。依据本试验结果，作者对牙鲆疾病防治中消毒剂的使用进行了探讨。     

SMM在实验性肾功能损害家兔体内的药物动力学研究

分析了SMM在健康家兔及肾损害兔体内的药物动力学过程。12只家兔分为A、B两组。A组为健康对照组,B组为肾功能损害病理模型组。A、B两组家兔均以140 mg/kg(SMM)剂量耳静脉注射SMM-Na,给药前心脏采血0.5 mL,作为空白对照。分别于给药后0.08、0.25、0.5、1、2、3、4、6 h各采血0.5 mL。以Annino法分析游离SMM血药浓度。结果显示,SMM在家兔体内药物动力学配置符合二室开放模型。药时曲线最佳方程为:C正常=13.910e-6.830t 32.569e-1.076t,C肾损害=15.748e-4.542t 27.473e-0.323t。肾损害时药动学参数与健康时的比较,α下降了33.49%;β下降了69.98%;t1/2α增加了41.03%;t1/2β增加了237.5%;AUC增加了33.49%;CLB下降了69.98%。表明家兔肾功能损害后,SMM在其体内消除显著变慢。提示在肾脏损害时应相应增大SMM给药间隔时间或减小给药剂量。     

牙鲆群体生化遗传学研究——Ⅰ.组织特异性研究

采用聚丙烯酰胺凝胶电泳技术,研究了AAT、EST、SOD、MDH、LDH和ME等位酶在牙鲆[Paralichthys olivaceus(T.et S.)]心脏、肌肉、鳃、眼睛、肾脏、肝脏、肠、脾、胃组织器官中表达,并分析了各种酶的等位酶位点表达以及酶谱表型。研究结果表明EST、SOD、MDH和ME 4种等位酶在不同组织中表达相同,AAT、LDH 2种等位酶在不同组织中表达差异,可能是受不同基因位点或同一基因位点不同等位基因控制的结果,与各组织完成特有生化代谢活动有关。     

阿莫西林注射用混悬液及其在猪体内的药物动力学研究

以阿莫西林为原料,注射用大豆油为溶媒,成功研究出阿莫西林注射用混悬液,并对制剂进行了稳定性研究。所有参试样品的相对含量、外观性状、粒度、分解产物等指标均无明显变化,表明该制剂对光、热稳定。选用5头健康猪进行了药物动力学研究,按15mg/kgB.W的阿莫西林剂量肌内注射,药时曲线符合一级吸收二室模型,主要动力学参数为:Tmax=0 53±0 17h,Cmax=12 33±0 47μg/ml,AUC=79 62±4 32(μg/ml)h,T1/2β=33 62±4 06h。结果表明,阿莫西林注射用混悬液在猪体内吸收缓慢,持效时间长。临床应用48h给药1次仍能维持对常见病原菌的有效血药浓度。